Reconstructing early transmission networks of SARS-CoV-2 using a genomic mutation model

Zool Res. 2023 May 18;44(3):494-504. doi: 10.24272/j.issn.2095-8137.2022.535.

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has greatly damaged human society, but the origins and early transmission patterns of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen remain unclear. Here, we reconstructed the transmission networks of SARS-CoV-2 during the first three and six months since its first report based on ancestor-offspring relationships using BANAL-52-referenced mutations. We explored the position (i.e., root, middle, or tip) of early detected samples in the evolutionary tree of SARS-CoV-2. In total, 6 799 transmission chains and 1 766 transmission networks were reconstructed, with chain lengths ranging from 1-9 nodes. The root node samples of the 1 766 transmission networks were from 58 countries or regions and showed no common ancestor, indicating the occurrence of many independent or parallel transmissions of SARS-CoV-2 when first detected (i.e., all samples were located at the tip position of the evolutionary tree). No root node sample was found in any sample ( n=31, all from the Chinese mainland) collected in the first 15 days from 24 December 2019. Results using six-month data or RaTG13-referenced mutation data were similar. The reconstruction method was verified using a simulation approach. Our results suggest that SARS-CoV-2 may have already been spreading independently worldwide before the outbreak of COVID-19 in Wuhan, China. Thus, a comprehensive global survey of human and animal samples is essential to explore the origins of SARS-CoV-2 and its natural reservoirs and hosts.

新冠肺炎大流行给人类社会造成了巨大的损失,但新冠病毒的起源和早期传播模式仍不清楚。该研究使用BANAL-52做为参考序列,推断出新冠病毒样本之间的“亲代-后代”关系,并重建了新冠病毒首次报道后前三个月和前六个月的传播网络。该研究旨在探索这些新冠病毒早期样本在其进化树上的位置(根部,中部或顶部)。使用前三个月数据,该研究重建了6 799条传播链和1766个传播网络,链长为1-9个节点。1766个传播网络的根节点样本来自58个国家或地区,没有共同祖先样本,表明新冠病毒在首次被发现之前就已经出现了大量的独立或平行的传播网络,即早期采集的新冠病毒样本处于进化树的顶端。自2019年12月24日以来,前15天采集的样本( n=31,全部来自中国大陆)均不是网络根结点样本。使用前6个月数据的结果或使用RaTG13做为参考序列的结果类似。该研究还通过使用计算机模拟方法验证了传播网络重建方法的可靠性。该研究结果表明,在武汉发现新冠肺炎之前,新冠病毒可能就早已在全球多地独立传播。因此,有必要在全球范围内调查人类或动物样本以寻找新冠病毒的来源及其自然宿主。.

Keywords: Ancestor-offspring relationship; Back mutation; De novo mutation; SARS-CoV-2; Secondary mutation; Transmission chain; Transmission network.

MeSH terms

  • Animals
  • COVID-19* / veterinary
  • Genomics
  • Humans
  • Mutation
  • Phylogeny
  • SARS-CoV-2* / genetics

Grants and funding

This study was supported by the Ministry of Science and Technology of the People’s Republic of China (2021YFC0863400) and Institute of Zoology, Chinese Academy of Sciences (E0517111, E122G611)